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Synthesis of Poly(acyclic orthoester)s: Acid-Sensitive Biomaterials for Enhancing Immune Responses of Protein Vaccine
Authors:Yumeng Xing  Zunkai Xu  Tao Liu  Prof. Linqi Shi  Prof. Daniel Kohane  Prof. Shutao Guo
Affiliation:1. Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071 China;2. Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115 USA
Abstract:While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.
Keywords:Biomaterialien  Wirkstofftransport  Ester  Nanopartikel  Polymere
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